The Clinical and Experimental Therapeutics Program (Program 4) is a cohesive, integrated program supported by $7,523,204 (annual direct costs) in peer-reviewed funding, with $3,613,675 from the NCI. There are 47 members representing nine departments. Of the total 747 member peer-reviewed publications during the current grant cycle, 216 (29%) represent intraprogrammatic, and 145 (19%) represent interprogrammatic collaborations. The overall goal of the Program is to foster interaction between basic and clinical investigators that will result in innovative and effective therapies for cancer patients. The translational nature of much of the work emanating from this program and the leadership role assumed by many program faculty in studies conducted by national clinical trials cooperative groups illustrates the impact of this program in developing new therapies for oncology. The Program has a long-standing focus on drug development at all phases of clinical testing and a strong pharmacogenetic component. Trials span the gamut from preclinical development to investigator-initiated Phase I clinical trials, to Phase II trials in the regional Phase II network to Phase III studies within CALGB. They incorporate correlative laboratory studies including pharmacokinetic studies, genotyping studies, population pharmacology, pharmacogenetic studies, and the measurement of surrogate endpoints. Clinical trials are conducted by multidisciplinary teams comprised of a group of clinical investigators representing Medical Oncology, Radiation Oncology, Pathology, and appropriate surgical specialties. Clinical efforts focus on studies of new drugs (cytotoxic or cytostatic) with clinical and translational endpoints, modulation of current chemotherapy, sequencing of multidisciplinary treatment, organ preservation, transplantation, and treatment intensification as strategies to increase cure rates and response. Imaging, surgical, and pathology support are integrated into the Program. The scientific goals are (1) to foster interaction between basic and clinical investigators that will result in innovative and effective therapies;(2) to integrate new drugs into the development of multimodality therapies for patients with advanced solid tumors;and (3) to pursue a broad program of preclinical, translational, and clinical research in pharmacogenetics and pharmacology.